This invention relates to a process for producing doxorubicin (adriamycin), and derivatives of doxorubicin, through a novel synthesis of daunomycinone and its derivatives. These mycinones can be coupled by known methods to daunosamine to produce doxorubicin and its corresponding derivatives.
It is known that doxorubicin is isolated from Streptomyces peucetius. A suitable process for this isolation is described by F. Arcamone, in "Duxorubicin Anticancer Antibiotics," (Academic Press, New York (1981). Moreover, synthetic routes to doxorubicin are known and these are summarized, for example, by F. Arcamone (loc. cit.), K. Krohn, Angew. Chem. Int. Ed. Engl., volume 25 (1986), page 790 and Tetrahedron, volume 46 (1989), page 291 and T. R. Kelly, Tetrahedron Symposium-in-Print, volume 40 (1984), pages 4537-4793.
A representative prior art procedure for converting daunomycinone to adriamycin is that proposed by Arcamone et al., U.S. Pat. No. 3,803,124. The prior art methods of obtaining daunomycinone have the disadvantage of being expensive.